A Phase I Study to Evaluate the Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Adults with Renal Impairment

TPN171, a phosphodiesterase 5 inhibitor, is under development for the treatment of male erectile dysfunction and pulmonary arterial hypertension in China. To investigate the pharmacokinetic properties and safety of TPN171 in individuals with severe renal impairment and normal renal function, an open-label, single-dose, parallel-group phase 1 study was conducted in 8 participants with severe renal impairment (glomerular filtration rate within 15-29 mL/min) and 8 participants having normal renal function, who received TNP171 tablets (10 mg) in the fasting state. As compared with those with normal renal function, the geometric mean ratios for maximum plasma concentration (Cmax), the area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t), and AUC extrapolated to infinite time (AUC0-infinity) were 74.3%, 138%, and 137%, respectively. Elimination half-life was prolonged and clearance was decreased in severe renal impairment group. The adverse reaction rate showed no significant difference. All adverse events were mild intensity, and no participant was discontinued in this study. In conclusion, TPN171 can be cautiously used in patients with mild to severe renal impairment.